ArticleFluids and barriers of the CNS2021
Reduction in pericyte coverage leads to blood-brain barrier dysfunction via endothelial transcytosis following chronic cerebral hypoperfusion.
Article in Fluids and barriers of the CNS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 96 citations in OpenAlex.
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- Article
- Pathophysiological Role of Perivascular Macrophages in Blood-Brain Barrier Dysfunction Induced by Cerebral Hypoperfusion in Mice.Neurochemical research · 2026Article
- Reduced endothelial TAK1 impairs vascular integrity in cerebral small vessel diseaseStroke and vascular neurology · 2026Article
- Hyperlipidemia induces hippocampal inflammation and loss of vascularity and can be rescued by silencing RIPK1.Scientific reports · 2026Article
- Epigenetic Regulation of the NET Formation-Blood-Brain Barrier Axis in Ischemic Stroke: Mechanisms, Therapeutic Targets and Translational Perspectives.Neurology international · 2026Review
- Chemogenetic modulation of CNS pericytes: Impact on pericyte CaMolecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Ultra-widefield OCTA assessment of retinal and choroidal microcirculation in cerebral small vessel disease.Scientific reports · 2026Article
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Aquaporin-4 deficiency induced white matter injury via upregulated complement component 3 in cerebral small vessel disease.Journal of neuroinflammation · 2026Article
- Notch signaling activation reduces vesicular endocytosis in human pluripotent stem cell-derived CNS-like endothelial cells.Fluids and barriers of the CNS · 2026Article
- Morphological and transcriptomic change of brain pericytes by lipopolysaccharide treatment.Frontiers in neural circuits · 2026Article
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- Pathophysiological and Etiological Corroborations for the Mechanistic Design of Intranasal Therapies in Glioblastoma Multiforme.Current pharmaceutical design · 2026Review
- Expression differences and diagnostic efficacy of core plasma biomarkers in Alzheimer's disease, cerebral small vessel disease and healthy adults.Frontiers in neurology · 2026Article
- Mitochondrial control of blood-brain barrier homeostasis in neuroinflammatory psychiatric disorders.Frontiers in molecular neuroscience · 2026Review
- Pericytes as key mediators of microenvironmental signaling crosstalk: implications in vascular diseases and cancer.Frontiers in cell and developmental biology · 2026Review
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
- Associations of carotid flow velocity with cerebral perfusion and cerebral small vessel disease: a community-based prospective study.European journal of medical research · 2025Article
- Crossing Pathological Boundaries: Multi-Target Restoration of the Neurovascular Unit in Alzheimer's and Vascular Dementia-From Modern Therapeutics to Traditional Chinese Medicine.Aging and disease · 2025Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic cerebral hypoperfusion (CCH) is the leading cause of cerebral small vessel disease (CSVD). CCH is strongly associated with blood-brain barrier (BBB) dysfunction and white matter lesions (WMLs) in CSVD. However, the effects of CCH on BBB integrity and components and the cellular and molecular mechanisms underlying the effects of BBB dysfunction remain elusive. Whether maintaining BBB integrity can reverse CCH-induced brain damage has also not been explored.
methodsIn this study, we established a rat model of CSVD via permanent bilateral common carotid artery occlusion (2VO) to mimic the chronic hypoperfusive state of CSVD. The progression of BBB dysfunction and components of the BBB were assessed using immunostaining, Western blotting, transmission electron microscopy (TEM) and RNA sequencing. We also observed the protective role of imatinib, a tyrosine kinase inhibitor, on BBB integrity and neuroprotective function following CCH. The data were analyzed using one-way or two-way ANOVA.
resultsWe noted transient yet severe breakdown of the BBB in the corpus callosum (CC) following CCH. The BBB was severely impaired as early as 1 day postoperation and most severely impaired 3 days postoperation. BBB breakdown preceded neuroinflammatory responses and the formation of WMLs. Moreover, pericyte loss was associated with BBB impairment, and the accumulation of serum protein was mediated by increased endothelial transcytosis in the CC. RNA sequencing also revealed increased transcytosis genes expression. BBB dysfunction led to brain damage through regulation of TGF-β/Smad2 signaling. Furthermore, imatinib treatment ameliorated serum protein leakage, oligodendrocyte progenitor cell (OPC) activation, endothelial transcytosis, microglial activation, and aberrant TGF-β/Smad2 signaling activation.
conclusionsOur results indicate that reduced pericyte coverage leads to increased BBB permeability via endothelial transcytosis. Imatinib executes a protective role on the BBB integrity via inhibition of endothelial transcytosis. Maintenance of BBB integrity ameliorates brain damage through regulation of TGF-β/Smad2 signaling following CCH; therefore, reversal of BBB dysfunction may be a promising strategy for CSVD treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.